5-fluoro-N²-[3-methoxy-5-(5-methyl-1H-tetrazol-1-yl)phenyl]-N⁴-[(1,2,2,6,6-pentamethylpiperidin-4-yl)methyl]pyrimidine-2,4-diamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-fluoro-N²-[3-methoxy-5-(5-methyl-1H-tetrazol-1-yl)phenyl]-N⁴-[(1,2,2,6,6-pentamethylpiperidin-4-yl)methyl]pyrimidine-2,4-diamine
• 英文别名: 5-fluoro-2-N-[3-methoxy-5-(5-methyltetrazol-1-yl)phenyl]-4-N-[(1,2,2,6,6-pentamethylpiperidin-4-yl)methyl]pyrimidine-2,4-diamine
• 化学式: C₂₄H₃₄FN₉O
• 分子量: 483.592
• InChiKey: WZHYKOZXHPTUKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1,2,2,6,6-五甲基-4-哌啶酮 在 盐酸 、 lithium aluminium tetrahydride 、 N,N-二异丙基乙胺 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙酸乙酯 、 异丙醇 、 叔丁醇 为溶剂， 反应 22.0h， 生成 5-fluoro-N²-[3-methoxy-5-(5-methyl-1H-tetrazol-1-yl)phenyl]-N⁴-[(1,2,2,6,6-pentamethylpiperidin-4-yl)methyl]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Optimization of 2,4-diamino-5-fluoropyrimidine derivatives as protein kinase C theta inhibitors with mitigated time-dependent drug–drug interactions and P-gp liability

  摘要：

  Protein kinase C theta (PKC theta) plays a critical role in T cell signaling and has therapeutic potential for T cell-mediated diseases such as transplant rejection and rheumatoid arthritis. Here, a series of 2,4-diamino-5-fluoropyrimidine derivatives were prepared and evaluated for their inhibition of PKC theta. Of these compounds, 14f was found to exhibit potent PKC theta inhibitory activity and significantly weak CYP3A4 time-dependent inhibition (TDI) and P-glycoprotein (P-gp) liability. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.050

文献信息

• Optimization of 2,4-diamino-5-fluoropyrimidine derivatives as protein kinase C theta inhibitors with mitigated time-dependent drug–drug interactions and P-gp liability
  作者：Shigeki Kunikawa、Akira Tanaka、Koichiro Mukoyoshi、Shinya Nagashima、Hiroaki Tominaga、Noboru Chida、Mamoru Tasaki、Fumiyuki Shirai

  DOI：10.1016/j.bmc.2015.04.050

  日期：2015.7

  Protein kinase C theta (PKC theta) plays a critical role in T cell signaling and has therapeutic potential for T cell-mediated diseases such as transplant rejection and rheumatoid arthritis. Here, a series of 2,4-diamino-5-fluoropyrimidine derivatives were prepared and evaluated for their inhibition of PKC theta. Of these compounds, 14f was found to exhibit potent PKC theta inhibitory activity and significantly weak CYP3A4 time-dependent inhibition (TDI) and P-glycoprotein (P-gp) liability. (C) 2015 Elsevier Ltd. All rights reserved.